Table 1.
Completed trials of targeted therapies in metastatic CRC with a BRAFV600E mutation
| Trial | Reference | Trial design | Intervention arm | Control arm | Summary of results |
|---|---|---|---|---|---|
| NCT00405587 | Kopetz et al8 | Open label, Phase II, single arm | Vemurafenib 960 mg BID (N=21) | NA | One partial response (5%); seven patients with stable disease. Median PFS of 2.1 months |
| NCT01072175 | Corcoran et al44 | Open label, Phase I/II single arm | Dabrafenib (150 mg BID) plus trametinib (2 mg daily) (N=43) | NA | Five patients (12%) sustained a partial response or better; 24 patients (56%) with stable disease |
| NCT01750918 | Corcoran et al46 | Open label, Phase I/II | Dabrafenib 150 mg BID, trametinib 2 mg daily, and panitumumab 6 mg/kg every 14 days (N=35) | Dabrafenib 50 mg BID and panitumumab 6 mg/kg every 14 days (N=20) | Response rate in three-drug combination was 26%, with an additional 57% of patients achieving stable disease |
| NCT01719380 | van Geel et al50 | Phase Ib dose escalation | Encorafenib + cetuximab + alpelisib, with escalating doses (N=28) | Encorafenib + cetuximab (N=26) | Overall response rates of 19% and 18% were confirmed in two-drug and three-drug combinations, respectively. Median PFS was 3.7 and 4.2 months for two-drug and three-drug combinations, respectively |
| NCT02164916 | Kopetz et al52 | Randomized Phase II | Irinotecan (180 mg/m2) and cetuximab (500 mg/m2) every 14 days, plus vemurafenib (960 mg PO BID) (N=54) | Irinotecan (180 mg/m2) and cetuximab (500 mg/m2) every 14 days (N=52) | Median PFS 4.4 vs 2.0 months (HR 0.42; 95% CI 0.26–0.66; P<0.001). ORR 16 vs 4% (P=0.09). Disease control rate of 67 vs 22% (P<0.001) |
Abbreviations: BID, twice a day; CRC, colorectal cancer; HR, hazard ratio; NA, not applicable; ORR, overall response rate; PFS, progression-free survival; PO, by mouth.